EBF1-Correlated Long Non-coding RNA Transcript Levels in 3rd Trimester Maternal Blood and Risk of Spontaneous Preterm Birth

Biomarkers associated with spontaneous preterm birth (sPTB) before labor onset could aid in prediction, triage, and stratification for testing interventions. In this study we examined maternal bloodEBF1-correlated long non-coding RNAs (lncRNAs) in relation to sPTB. We retrieved all lncRNA transcripts from a public gene expression dataset (GSE59491) derived from maternal blood in trimesters 2 and 3 from a Canadian cohort with a matched set of sPTB (n = 51) and term births (n = 106). LncRNA transcripts differentially expressed (limma moderatedt-tests) in sPTB vs. term were tested for correlations (Pearson) withEBF1mRNA levels in the same blood samples. Using logistic regression,EBF1-correlated lncRNAs were divided into tertiles and assessed in relation to odds of sPTB. Two lncRNA transcripts in the 3rd trimester maternal blood were differentially expressed between sPTB and term births (allp < 0.001 and FDR < 0.250) and positively and negatively correlated withEBF1mRNA levels. They were as follows: (1)LINC00094 r = 0.196 (95% CI: 0.039 to 0.344),p = 0.015, and BH adjustedp = 0.022 and (2)LINC00870 r = - 0.303 (95% CI: - 0.441 to - 0.152),p < 0.001, and BH adjustedp < 0.001. As compared with term births, sPTBs were more likely to be in the highest tertile ofLINC00870(odds ratio (OR) = 4.08 (95% CI 1.60, 10.40),p = 0.003) and the lowest tertile ofLINC00094(OR = 5.16 (95% CI 1.96, 13.61),p < 0.001). Two sPTB-associatedEBF1-correlated lncRNAs (LINC00870andLINC00094) had multiple potential enhancers containing EBF1 binding site(s). Our current findings, along with previous reports linkingEBF1and sPTB, motivate additional research on theEBF1gene-related gene expression and regulation in relation to sPTB within other cohorts and within laboratory-based models.